New understanding of hearing loss

A major breakthrough in the understanding of hearing and noise-induced hearing loss has been made by hearing scientists from the Centre for Brain Research.

Scientists from The University of Auckland, the University of New South Wales in Sydney, and the University of California in San Diego have collaborated for nearly 20 years on this research.

“This work represents a paradigm shift in understanding how our ears respond to noise exposure,” says Professor Peter Thorne from Centre for Brain Research at The University of Auckland, who is one of the co-authors of two papers published recently in the prestigious journal, the Proceedings of the National Academy of Sciences (PNAS).

“We demonstrate that what we traditionally regard as a temporary hearing loss from noise exposure is in fact the cochlea of the inner ear adapting to the noisy environment, turning itself down in order to be able to detect new signals that appear in the noise,” he says.

After the noise is turned off, hearing remains temporarily dull for some time while it readjusts to the lack of noise.

“Clinically, this is what we measure as a temporary hearing loss,” says Professor Thorne.  “This has always been regarded as an indication of noise damage rather than, in our new view, a normal physiological process.”

The research team includes Dr Srdjan Vlajkovic, who has shown that these changes are due to a molecular signalling pathway in the cochlea, mediated by a chemical compound called ATP, released by the cochlear tissue with noise and activating specific ATP receptors in the cochlear cells.

“Interestingly, if the pathway is removed, such as by genetic manipulations, this adaptive mechanism doesn’t occur and the ear becomes very vulnerable to longer term noise exposure and the effects of age, eventually resulting in permanent hearing loss. In other words the adaptive mechanism also protects the ear,” says Professor Thorne, who is a Deputy-Director of the Centre for Brain Research.

The second paper, done in collaboration with United States colleagues, reveals a new genetic cause of deafness in humans which involves exactly the same mechanism.

People (two families in China) who had a mutation in the ATP receptor showed a rapidly progressing hearing loss which was accelerated if they worked in noisy environments.

“This work is important because it shows that our ears naturally adapt to their environment, a bit like pupils of the eye which dilate or constrict with light, but over a longer time course,” Professor Thorne says.

This inherent adaptive process also provides protection to the ear from noise and age-related wear and tear. If people don’t have the genes that produce this protection, then they are more likely susceptible to developing hearing loss.

“This may go some way to explaining why some people are very vulnerable to noise or develop hearing loss with age and others don’t,” he says.

“Our research demonstrates that what we have always thought was temporary noise damage (ie the temporary hearing loss experienced in night clubs or a day’s work in factories), may not be this, but instead, is the ear regulating its sensitivity in background noise. “

“Although our research suggests that our hearing adapts in some noise environments, this has limits,” says Professor Thorne.  “If we exceed the safe dose of noise, our ears can still be damaged permanently despite this apparent protective mechanism.”

“People need to protect their ears from constant noise exposure to prevent hearing loss and this is particularly important in the workplace and with personal music devices which can deliver high sound levels for long periods of time,” he says.

CBR scientists boosted with support from AMRF

The Auckland Medical Research Foundation has announced its latest round of grants, with several innovative projects funded in the Centre for Brain Research. The research will help to develop new treatments for Huntington’s disease, obesity, visual defects, and hearing loss.

– $141,154
Dr Johanna Montgomery, Dr Ailsa McGregor Dept of Physiology & Centre for Brain Research, The University of Auckland

All neurodegenerative diseases have direct or indirect effects on synapses in the brain. Therefore a major step towards understanding what goes wrong in the diseased brain is to understand how synapse function is altered by disease. In this proposal we seek to determine the source of synapse dysfunction in Huntington’s Disease (HD). Previous work on HD mouse models has shown that receptors on the surface of neurons are mis-localised, inducing changes in synapse function. Here we will focus on two synaptic proteins, bSAP97 and aSAP97, which we have recently shown can control the distribution of receptors on neurons (Li et al., 2011, J. Physiology 589, 4491-4510). We will utilise a cellular and an animal model of HD to determine whether changing the expression levels of bSAP97 or aSAP97 can rescue normal receptor distribution, and whether this subsequently rescues normal synapse function. These cellular data will identify whether a and/or bSAP97 are part of the pathological signature for HD and also whether they could be potential therapeutic targets.

– $97,250 Mr Nabin Paudel
Dept of Optometry & Vision Sciences, The University of Auckland

Newborn babies commonly experience low blood sugar, a condition known as neonatal hypoglycaemia.  As glucose is the brain’s main energy source, this condition may impair neurological function, however, at present, very little is known about the effect of neonatal hypoglycaemia on brain development.  As a consequence, the level of neonatal hypoglycaemia that requires treatment in early infancy is currently unknown.  This PhD project forms part of a large multidisciplinary study known as the Children with Hypoglycemia and their Later Development (the CHYLD study) which aims to assess the developmental effects of neonatal hypoglycaemia in a cohort of 500 children whose blood glucose levels were measured continuously for several days after birth.  The aim of this specific project is to assess visual function in these children at the ages of 2 and 4.5 years.  Vision is of particular interest as neonatal hypoglycaemia may preferentially affect visual brain areas.  The assessments include a range of vision tests targeting specific regions of the visual cortex and will therefore provide new insights into the effect of neonatal hypoglycaemia on the rate and extent of visual cortex development.  The study will also provide important information regarding the treatment and management of hypoglycaemia in newborns.

– $166,636
Dr Kathy Mountjoy, Dr Ailsa McGregor Dept of Physiology, The University of Auckland

Stress, weight gain and glucose metabolism are influenced by a group of hormones called melanocortin peptides. These peptides comprise chains of amino acids, of varying length, and are derived from one large precursor protein found in the brain and pituitary gland, called proopiomelanocortin (POMC). Special enzymes chop-up POMC to form the melanocortin peptides, according to the body’s requirement. We have developed a mouse that lacks a particular 13 amino acid melanocortin peptide called adrenocorticotropic hormone (ACTH1-13). These mice can be used to study what effects of ACTH1-13 on physiological function. The mice appear normal until they reach puberty and then they develop obesity, but not diabetes. Treatment of these obese mice with ACTH1-13 or a natural variant that is slightly chemically altered, called -melanocyte stimulating hormone (-MSH), reduced mouse body weight and fat mass when mice were fed a normal diet. In light of the worldwide obesogenic environment, we will now test whether obesity and diabetes in these mice is exacerbated by a feeding a high-fat diet, and whether melanocortin hormone treatment can reverse obesity while animals feed on a high-fat diet. These studies should aid the development of improved tests and treatments for obesity and type 2 diabetes.

– $146,752 Dr Srdjan Vlajkovic, Prof Peter Thorne, Dr Detlev Boison, Prof Gary Housley
Dept of Physiology, The University of Auckland

Hearing loss affects 10-13% of New Zealanders and this prevalence will increase with the aging population. Exposure to noise and drugs toxic to the inner ear are major contributing factors to this disability. Prosthetic rehabilitation via hearing aids and cochlear implants is the only current treatment for hearing loss. Hence, it is essential to develop therapies that can ameliorate or repair injury to the delicate structures of the inner ear. We have shown that hearing loss in experimental animals exposed to traumatic noise can be substantially restored by administration of drugs acting on adenosine receptors. Here we propose a set of studies that will utilize transgenic mice that lack genes for the two main types of adenosine receptors found in the inner ear to assess their responses to aging, noise stress and drug toxicity. This is critical translational research for therapeutic management of noise, age and drug-induced hearing loss.